Risk Stratification of Gastrointestinal Stromal Tumors by Nanostring Gene Expression Profiling

Abstract PurposeThe risk assessment classification schemes for gastrointestinal stromal tumors (GIST) includes tumor site, size, mitotic count and variably tumour rupture. Heterogeneity in high risk GIST poses limitations for current classification schemes. Objective This study aims to demonstrate the clinical utility of risk stratification by gene expression profiling (GEP) using Nanostring technology. MEthodFifty-six GIST cases were analyzed using a 231 gene expression panel. GEP results were correlated with clinical and pathological data. The prognostic performance was assessed in 34 patients with available survival data using ROC curves, Kaplan Meier Survival curves and compared with traditional risk assessment schemes. Results Volcano plot analysis identified seven genes with significantly higher expression (FDR < .05) in high risk than in non-high risk tumors, namely, TYMS, CDC2, TOP2A, CCNA2, E2F1, PCNA, and BIRC5. Together, these transcripts exhibited significantly higher expression in high risk tumors than in intermediate ( P < .001), low ( P < .001), and very low ( P = 0.01) risk tumors. Receiver operating characteristic curve analysis demonstrated area under the curve (AUC) to be 0.861 for the separation of high risk and non-high risk tumors. Kaplan-Meier survival analysis demonstrated improved risk stratification (log-rank test P < .001) compared to the current risk assessment classification ( P = 0.18). Conclusion In addition to current clinical and histology-based risk classification for patients with GIST, gene expression may offer complementary prognostic information.